Send Orders of Reprints at [email protected] The Open Neurology Journal, 2012, 6, (Suppl 1-M11) 179-186 179 Open Access Damage of Collagen and Elastic Fibres by Borrelia Burgdorferi – Known and New Clinical and Histopathological Aspects Kurt E. Müller* Medical Practice for Dermatology, Venerology, Occupational Dermatology and Environmental Medicine, Kempten, Bavaria, Germany Abstract: Lyme Borreliosis, or Lyme’s disease, manifests itself in numerous skin conditions. Therapeutic intervention should be initiated as soon as a clinical diagnosis of erythema migrans is made. The histopathology of some of the skin conditions associated with Lyme Borreliosis is characterised by structural changes to collagen, and sometimes also elastic fibres. These conditions include morphea, lichen sclerosus et atrophicus and acrodermatitis chronica atrophicans. More recently, further skin conditions have been identified by the new microscopic investigation technique of focus floating mi- croscopy: granuloma annulare, necrobiosis lipoidica, necrobiotic xanthogranuloma, erythema annulare centrifugum, inter- stitial granulomatous dermatitis, cutaneous sarcoidosis and lymphocytic infiltration; these conditions also sometimes cause changes in the connective tissue. In the case of ligaments and tendons, collagen and elastic fibres predominate struc- turally. They are also the structures that are targeted by Borrelia. The resultant functional disorders have previously only rarely been associated with Borreliosis in clinical practice. Ligamentopathies and tendinopathies, spontaneous ruptures of tendons after slight strain, dislocation of vertebrae and an accumulation of prolapsed intervertebral discs as well as ossifi- cation of tendon insertions can be viewed in this light. Keywords: Lyme Borreliosis, collagen fibres, elastic fibres, skin, connective tissue, tendons, ligaments, diverticulum. INTRODUCTION annulare centrifugum [13], microbial eczema [Müller: un- published], erythema nodosum [3; Müller unpublished], Lyme Borreliosis causes skin symptoms at all stages of pityriasis lichenoides chronica [24], acrodermatitis papulosa the disease [1-3]. The most common skin conditions associ- [Gianotti-Crosti syndrome], pityriasis rosea [21] perifollicu- ated with Lyme Borreliosis are morphea [1, 4-10], lichen litis [24], panniculitis [25,26], lymphocytoma [synonym: sclerosus et atrophicus [LSA; 1, 4-6, 10-12], and acroderma- lymphadenosis cutis benigna [Bäfverstedt’s syndrome; 27- titis chronica atrophicans [ACA; 1, 6-8, 13], which possess 29], benign lymphocytic infiltration [Jessner-Kanof syn- an acute inflammatory stage followed by a chronic atrophic drome; [30,31], sarcoidosis [32], B-cell lymphoma [33], stage (Table 1-3). These skin conditions associated with pseudolymphoma [Müller: unpublished], Raynaud’s syn- Lyme Borreliosis are characterised by pronounced histopa- drome [34] and vasculitis racemosa [Müller; unpublished]. thological changes of the collagen fibres, but also occasion- This paper will deal with skin conditions that cause histopa- ally the elastic fibres in their connective tissue structures thological changes to the collagen and elastic fibres. [6,1,9,12,13]. The following also display similar disorders of their connective tissue: granuloma annulare, necrobiosis lipoidica and necrobiotic xanthogranuloma [1]. With the aid Focus Floating Microscopy (FFM) of a new histopathological technique, these skin conditions After the introduction of FFM, a number of dermatologi- have also been found to contain Borrelia [13-17]. In some cal conditions could be attributed to Lyme Borreliosis. FFM cases, LB was also detected in the connective tissue of pa- is a modified immunohistochemical investigation technique tients suffering from pseudopelade of Brocq [18], Sudeck’s in which several strategies are combined in order to be able dystrophy [19], hemifacial atrophy [20] and scleroedema of to identify microorganisms in tissue sections. In FFM, tissue Buschke [21]. sections are investigated in two planes: horizontally in a There are also other skin conditions that do not display serpentine-like pattern, as is usual in cytology, and vertically, any particular connective tissue changes and optionally may focussing through the entire thickness of the section (nor- occur as reactive skin conditions in Lyme Borreliosis. These mally 3-4 µm). The tissue section is stained bright red with include urticaria [22], erythema multiforme [23], erythema aminoethylcarbazol (AEC) and a light source is used that shines through the specimen approximately 10 times more strongly than usual. Thus a good contrast can be established *Address correspondence to this author at the Mozartstrasse 16, D 87435 between the microorganisms and the bright yellow collagen, Kempten, Germany; Tel: +49 (0)831 5126729; Fax: +49 (0)831 5409294; optimising identification of the pathogen [14]. E-mail: [email protected] 1874-205X/12 2012 Bentham Open 180 The Open Neurology Journal, 2012, Volume 6 Kurt E. Müller Table 1. Pathohistology of Morphea Early Phase Sclerotic Stage Oedematous swelling of collagen fibres Homogenised collagen fibre bundle Cell infiltration of lymphocytes, eosinophils and plasma cells Decrease in strength of fibrils Reduction in cell infiltrates Slit-like narrowing of vessels Loss of accessory structures of the skin Hyaline sclerotic transformation of corium Table 2. Pathohistology of Acrodermatitis Chronica Atrophicans Inflammatory Stage Atrophic Stage Oedematous swelling of hyalinised collagen fibres Atrophy with disappearance of elastic fibres Undulating or ribbon-like perivascular lymphocytic infiltrates Nests of Borrelia can be found in the collagen fibre bundles Subepidermal haemorrhagic blisters due to infiltration of blood Deposit of IgM, IgG, IgA, complement and fibrin Table 3. Pathohistology of Lichen Sclerosus et Atrophicus Initial Phase Late Phase Oedematous swelling of hyalinised collagen fibres Atrophy with disappearance of elastic fibres Undulating or ribbon-like perivascular lymphocytic infiltrates Foci of Bb can be found in the collagen fibre bundles Subepidermal haemorrhagic blisters due to infiltration of blood Deposit of IgM, IgG, IgA, complement and fibrin Cutaneous Manifestations of Lyme Borreliosis with In- homogenised collagen fibre bundles, a reduction in fibril volvement of the Connective Tissue strength, decrease in cell infiltration, slit-like vessels and loss of accessory structures of the skin in a hyaline sclerotic co- Morphea rium, in which only the arrector pili muscles are maintained Clinical finding: At the beginning a spot-like focus can [1, 6, 35]. Borrelia were detected in foci of morphea using be seen with slight inflammatory erythema radiating out- FFM [9]. wards on all sides. It can occur in isolation or in groups. The erythema gradually completely disappears in the centre into Acrodermatitis Chronica Atrophicans (ACA; Herx- a disc-like, ivory-coloured hardened area, that is surrounded heimer’s Disease) by a bluish-violet, lilac-coloured ring [1,7]. Atrophy devel- ops in the late phase, which is a hyper-pigmented dirty grey- Clinical finding: ACA tends to occur over the large joints ish-brown colour at the edges but usually without pigment in and distal parts of the extremities. It can also be seen on the the centre. During this phase there may be a loss of hair and face and trunk. It initially causes an oedematous skin swell- sebaceous glands. Morphea tends to occur on the trunk, less ing with slight erythema. Thread-like erythema may also commonly on the extremities. The foci may develop indi- develop on the extremities, characterised as ulnar striations vidually and be disseminated but also merge into patches or on the forearms and tibial striations on the legs. As there are become generalised and are then difficult to differentiate usually no subjective symptoms during this phase, early from scleroderma [1, 4-6, 10, 35, 36]. Atrophoderma of ACA of stage 1 Borreliosis usually goes unnoticed. In stage Pierini and Pasini [37, 38] is now considered to be an abor- 2 there is pronounced atrophy of the skin, which becomes tive form of morphea [39, 40]. thin, flaccid and creases like cigarette paper. The following symptoms then develop: hair loss, telangiectasias, varicose Histopathology (Table 1): Two phases can be distin- veins and altered pigmentation [1, 3, 8, 35]. guished histologically. The early phase is associated with an oedematous swelling of the collagen fibres and cell infiltra- Histopathology (Table 2): ACA starts with an inflamma- tion of lymphocytes, eosinophilic granulocytes and plasma tory oedematous stage of the corium associated with perivas- cells. This is followed by the second, sclerotic stage with cular lymphohistiocytic cell infiltration and plasma cells. This turns into an atrophic stage, where swelling and ho- Damage of Collagen and Elastic Fibres by Borrelia Burgdorferi The Open Neurology Journal, 2012, Volume 6 181 mogenisation of the fibres and disappearance of collagen and quently - in 92.7% of cases (38/41) - than in the atrophic late elastic fibres is observed. This stage enables a differential stage where there was less inflammation – 26.7% of cases diagnosis to systemic scleroderma to be made, where the (4/15). elastic fibres are not affected. There is also narrowing of the corium with infiltration of lymphocytes, histiocytes and a Granuloma Annulare (GA) large number of plasma cells [1,3]. Borrelia were detected in 50 out of 51 patients with ACA [15]. FFM was more sensi- Clinical